title: Influence of variants of Fc gamma receptors IIA and IIIA on the American College of Rheumatology and European League Against Rheumatism responses to anti-tumour necrosis factor alpha therapy in rheumatoid arthritis.
abstract: OBJECTIVE
  Fc gamma receptor (Fc gammaR) polymorphism influences the affinity of the receptor for Ig, which may, in turn, affect the efficacy of Ig-based therapies. The relationship between functional single nucleotide polymorphisms (SNP) of the FCGR2A and FCGR3A genes and the response to anti-tumour necrosis factor (TNF)alpha therapy (infliximab) in patients with rheumatoid arthritis (RA) was assessed.
  
  
  METHODS
  A total of 91 patients with RA (89% female; 76.7% rheumatoid factor (RF) positive) starting therapy with infliximab were evaluated at 0, 6 and 30 weeks using the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) response criteria and the 28-joint Disease Activity Score (DAS28) was evaluated using three parameters, including C-reactive protein (CRP) (DAS28 3v-CRP) changes during the follow-up. Genotyping of FCGR2A-R131H and FCGR3A-F158V polymorphisms was performed by allele-specific PCR and PCR sequence-based typing, respectively. The chi(2) and Fisher exact tests were used to show differences in the outcome variables, and analysis of variance (ANOVA) to analyse the evolution of DAS28 3v-CRP. A generalised linear models multivariable analysis was also performed.
  
  
  RESULTS
  At week 6 of follow-up, the proportion of patients achieving 50% improvement as per ACR criteria (ACR50) and EULAR good responses were significantly higher among homozygotes of the low affinity FCGR3A allele (FF: 24.1% and VV-VF:2.2%; p = 0.003 and FF: 44.8% and VV-VF: 22.9%; p = 0.040, respectively). At week 30, homozygotes of the low affinity FCGR2A allele had a better ACR20 response (RR: 60% and HH-RH: 33.3%; p = 0.035). Changes in DAS28 3v-CRP during follow-up were consistent with those observed in ACR and EULAR responses.
  
  
  CONCLUSIONS
  The response to anti-TNFalpha treatment with infliximab in patients with RA is influenced by the FCGR2A and FCGR3A genotypes. This effect is observed at different times in the follow-up (6 and 30 weeks, respectively) indicating the dynamic nature of the Fc gammaR versus Ig interaction.
authors.affiliation: Rheumatology, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, School of Medicine, University of Barcelona, Barcelona, Spain. jcanete@clinic.ub.es
authors.forename: J D
authors.initials: JD
authors.lastname: Cañete
authors.forename: B
authors.initials: B
authors.lastname: Suárez
authors.forename: M V
authors.initials: MV
authors.lastname: Hernández
authors.forename: R
authors.initials: R
authors.lastname: Sanmartí
authors.forename: I
authors.initials: I
authors.lastname: Rego
authors.forename: R
authors.initials: R
authors.lastname: Celis
authors.forename: C
authors.initials: C
authors.lastname: Moll
authors.forename: J A
authors.initials: JA
authors.lastname: Pinto
authors.forename: F J
authors.initials: FJ
authors.lastname: Blanco
authors.forename: F
authors.initials: F
authors.lastname: Lozano
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017452:Receptors, IgG / Q000235:genetics*; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; C496124:FCGR3A protein, human; C080568:Fc gamma receptor IIA; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab